There is a critical need for the development of effective clinical treatments for stroke, transient ischemia attacks, vasospasm and related acute neurodegenerative conditions. Our research results have clearly implicated free radicals in the etiology of ischemic brain damage. We have demonstrated that certain spin-trapping compounds (STCs) including phenyl-tert-butyl nitrone (PBN), offer considerable protection to the brain from an ischemia/reperfusion-mediated injury if the STCs are administered before or even after (1hr) initiating reperfusion of the ischemia-reperfusion lesioned brain. Centaur Pharmaceutical, Inc. would like to capitalize on the commercial protocol of novel STCs for the treatment of stroke. We therefore propose to determine if selected novel STCs protect the gerbil brain from ischemia injury and test the STCs in their ability to protect the rat using the middle cerebral artery (permanent as well as reversible) model and in addition establish a direct relationship between in vivo neuroprotective effects and in vitro antioxidant and radical trapping activity of selected STCs lead compounds.